MBBS, MD , Physicians

1. BEWARE OF THE HYPE- ANTIOXIDANT
SUPPLEMENTS
PROF. (DR.) VIYATPRAJNA
ACHARYA MBBS, M.D.
Biochemistry

2. Diseases that find their roots in
oxidant injury
• The Modern epidemics : Hypertension, DM, CVS
diseases
• Cancer
• Degenerative diseases : Parkinsonism, Alzheimer’s
disease
• Skin diseases: Lichen planus, vitiligo
• Chronic inflammatory diseases: Rheumatoid
arthritis, Chronic ulcerative colitis, CGN
• Others: Autism, ARDS, retrolental fibroplasia, cataract
• Oxidative damage leads to early ageing too!

3. Few of my research
activities………
• Lipid peroxidation and hyperuricemia in
essential HTN
• Dyslipidaemia and oxidative stress in
hypothyroidism
• Oxidative stress & passive smoking
• Antioxidants and lipid peroxidation in HTN,
DM
• NO & MDA in HTN

4. So wheream I ledto??? Some anti-research!!!

5. Please
prescribe me
some
expensive
antioxidants

6. Why this happens?
• Wide availability of
information
• Media
• Internet
• No restriction over OCD
• Increased awareness
among people
• Increased life span
• Economy

7. What are ANTIOXIDANTS??
• Scavengers or stabilizers of free
radicals / ROS
• Prevent cell damage
• Prevent ageing
• They are often reducing agents

8. Oxidative stress
Disturbance of balance between the
production of free radicals and antioxidant
defenses
Oxidants can injure almost all biomolecules
Lipid peroxidation- damage to cell membrane
Oxidation of Sulfhydryl group of enzymes
DNA damage- mutagenesis
Protein- fragmentation
Polysaccharides- degradation

9. Sources of oxidants
Internally generated:
1. Leaks in ETC
2. Xanthine oxidase & Aldehyde oxidase-
generate superoxide anions & H2O2
3. Inflammatory cells- NADPH oxidase
4. Macrophages – NO
5 . Platelets & leucocytes –
Lipoxygenase
6. Peroxisome
7. CytochromeP450-xenobiotics
metabolism
8. Inflammation / Ischaemia/ reperfusion/
exercise

10. External sources:
Ionizing radiation- gamma and UV
rays
Light
Cigarette smoke
Drugs, pesticides, anaesthetics &
industrial solvents
Ozone

11. Process of Lipid Oxidation – Auto-oxidation
Initiation
RH + (reactive oxygen species) ·OH -->R· + H2O
Propagation
R· + O2 ------> ROO·
ROO· + RH ------> R· + ROOH
ROOH -------> RO· + HO-
Termination
R· + R· ------> RR
R· + ROO· ------> ROOR
ROO· + ROO· ------> ROOR + O2
It’s a chain reaction

12. Role of antioxidants
Preventive antioxidants
intercept oxidizing species
before damage can be done
Chain breaking
antioxidants slow or stop
oxidative processes after
they begin, by intercepting
the chain-carrying radicals

13. • Antioxidants can end the chain reaction
of forming new free radicals by
donating one of their own electrons.
• When antioxidants donate an electron
they do not become a free radical
because they are stable in either form.

14. Preventive antioxidants act by:
A.Deactivating metals, e.g. Transferrin,
ferritin, Desferal, EDTA, …
B.Removing hydroperoxides, e.g. catalase,
glutathione peroxidases, pyruvate, …
C.Quenching singlet oxygen, e.g. -carotene,
lycopene, bilirubin, …

15. Chain-breaking
antioxidants
• React with peroxyl radicals usually- ROO
A)Donor antioxidant, e.g. tocopherol,
ascorbate, uric acid, …- donate their
electrons
B)Sacrificial antioxidant, e.g. nitric oxide
– get themselves utilised to form a
newer product

16. Food sources of antioxidants
• Spices, herbs, essential
oils, cocoa, tea
• Dried foods
• Red wine
• Deeply pigmented fruits-
mango, pomegranate, fig
• Cooked vegetables-
cabbage, beetroot
• Vitamins- A, C, E

17. • Vitamin cofactors & minerals-
Coenzyme Q 10, Mn, I2
• Hormones- melatonin
• Carotenoids & terpenoid- alpha
carotene, astaxanthin, lutein,
Lycopene, Zeaxanthin
• Polyphenols & natural phenols- fruits,
legumes

18. Antioxidant supplements available

19. Dosage ???

20. All antioxidants can behave as Pro-
oxidants
Ascorbate
Reduces
ferric to
Ferrous
Fenton
reaction
OH. Radical
generation
Uric acid- efficient
scavenger of
Peroxynitrite
Aminocarbonyl
radical– an
intermediate
oLDL generation

21. • In higher oxygen tension beta carotene
produces isoprostane – pro-oxidant
• α- Tocopherol, most effective
antioxidant for LDL-C, acts as a pro-
oxidant in a lipid dispersion- it needs
other antioxidants
Beta carotene

22. Cardiovascular Mortality increased
by antioxidant supplements !!!
• 68 randomized trials with 232 606
participants (385 publications)- Goran
Bjelakovic et al conducted a meta-analysis
• Singly or combined beta carotene, Vit A & E
increased CV mortality- RR= 1.07, 1.16, 1.04
• Vit C & Selenium – need further study

23. • Women’s health study (10 years) – no
beneficial effect on CVS events and cancer rate
by intake of Vitamin E
• HOPE trial – increased heart failure rate &
hospitalization rate
• GISSI trial (Italy) – No beneficial effect on CVS
• French study – No effect with combinations
too
• Effect on Cancer – Mixed results; inconclusive
• Finland study- beta carotene increased death
due to lung cancer amongst heavy smokers
• SU.VI.MAX trial - ↑rate of skin cancer

24. Some good news for eyes
Age-Related Eye Disease Study (AREDS) (6 yr trial)-
With combinations of of vitamin C, vitamin E, beta-
carotene, and zinc – offered some protection against
age-related change in macular degeneration, but
NOT cataract

25. It’s big money!!
• UK alone - £300 million /
year on supplements
• US – 25 billion dollar
• India - ???

26. Why antioxidants fail ???
• Not all the dietary factors are known
• Other factors in natural sources may be
interfering- positively or negatively
• Confounding factors are not taken into
consideration
• In vivo and in vitro behaviour are different
• Combinations do matter
• Relationship between free radicals and
health yet to be clear
• “Hermesis”

27. Some Indian indigenous thinking –
need of the hour
Different ethnicity
Different genotype
Wide regional
variation
Dietary variation
Different cooking
pattern
Cost of antioxidants
Indigenous research
Regulations
Restriction on OCD

28. PUFA added with antioxidant
supplements- another myth in
Indian cooking
Who checks the
TAC of cooked
foods
Storage
conditions?
In vivo effects

29. Let’s stay close to nature

30. Jai hind!

31. References
1. Carr A, Frei B (1999). "Does vitamin C act as a pro-oxidant under
physiological conditions?". FASEB J. 13 (9): 1007–24.
2. Valko M, Morris H, Cronin MT (2005). "Metals, toxicity and oxidative
stress". Curr. Med. Chem. 12 (10): 1161–208.
3. Ristow, M. .; Zarse, K. . (2010). "How increased oxidative stress promotes
longevity and metabolic health: the concept of mitochondrial hormesis
(mitohormesis)". Experimental Gerontology 45 (6): 410–418.
4. Bjelakovic G, Nikolova D, Gluud L, Simonetti R, Gluud C (2007). "Mortality
in Randomized Trials of Antioxidant Supplements for Primary and
Secondary Prevention: Systematic Review and Meta-analysis". JAMA 297
(8): 842–57.
5. Tapia, P (2006). "Sublethal mitochondrial stress with an attendant
stoichiometric augmentation of reactive oxygen species may precipitate
many of the beneficial alterations in cellular physiology produced by
caloric restriction, intermittent fasting, exercise and dietary phytonutrients:
"Mitohormesis" for health and vitality". Medical Hypotheses 66 (4): 832–
43.
• Vincent. W. Bowry & Roland Stocker.Tocopherol-mediated peroxidation.
The prooxidant effect of vitamin E on the radical-initiated oxidation of human
low-density lipoprotein. J. Am. Chem. Soc., 1993, 115 (14), pp 6029–6044

32. For more ppt on Medical Biochemistry
please visit my website
www.vpacharya.com